Preliminary experimental study of urethral reconstruction Nith tissue engineering and RNA interference techniques

This study investigated the feasibility of replacing urinary epithelial cells with oral keratinocytes and transforming growth factor-β1 （TGF-β1） small interfering RNA （siRNA）-transfected fibroblasts seeded on bladder acellular matrix graft （BAMG） in order to reconstruct tissue-engineered urethra. Constructed siRNAs, which expressed plasmids targeting TGF-β1, were transfected into rabbit fibroblasts. The effective siRNA was screened out by RT-PCR and was transfected into rabbit fibroblasts again. Synthesis of type I collagen in culture medium was measured by enzyme-linked immuno sorbent assay （ELISA）. Autologous oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts were seeded onto BAMGs to obtain a tissue-engineered mucosa. The tissue-engineered mucosa was assessed morphologically and with the help of scanning electron microscopy. The TGF-β1 siRNA decreased the expression of fibroblasts synthesis type I collagen. Oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts were seeded onto sterilized BAMG to obtain a tissue-engineered mucosa for urethral reconstruction. The compound graft was assessed using scanning electron microscope. Oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts had a good compatibility with BAMG. The downregulation of fibroblasts synthesis type I collagen expression by constructed siRNA interfering TGF-β1 provided a potential basis for genetic therapy of urethral scar. Oral keratinocytes and TGF-β1 siRNA-transfected fibroblasts had good compatibility with BAMG and the compound graft could be a new choice for urethral reconstruction.

Sustainable functional urethral reconstruction:Maximizing early continence recovery in robotic-assisted radical prostatectomy

Objective:To evaluate the safety profile and short-term functional outcome of sustainable functional urethral reconstruction(SFUR)in robotic-assisted radical prostatectomy(RARP).Methods:One hundred and sixty-two consecutive prostate cancer patients who underwent RARP were retrospectively analyzed,in which 53 had undergone SFUR while the other 109 had undergone conventional RARP procedures.Immediate,2-week,1-month and 3-month continence recovery and other perioperative data were compared to evaluate short-term surgical and functional outcome.Results:The median age was 68 and 67 years in the experimental group and control group,respectively(pZ0.206),with a median prostate-specific antigen(PSA)of 13.6 ng/mL(interquartile range[IQR],8.46e27.32 ng/mL)in the experimental group and 13.84 ng/mL(IQR,9.12e26.80 ng/mL)in control group(pZ0.846).Immediate,2-week,1-month and 3-month continence recovery rates between the groups were 34.0%vs.3.7%,50.9%vs.14.7%,62.3%vs.27.5%,and 79.2%vs.63.3%(all p<0.05).The morphological changes made by the new reconstruction technique were maintained on magnetic resonance imaging(MRI)3 months postoperatively.Nerve-sparing procedures and adoption of the new reconstruction technique were significantly relevant to continence recovery on logistics regression model(p<0.001).Conclusions:SFUR is a safe and easy-to-handle modification that may contribute to early continence return for RARP.Long-term follow-up and prospective studies are required to further evaluate its value in postoperative quality-of-life improvement.

Management of complex and redo cases of pelvic fracture urethral injuries

Objectives:Pelvic fracture urethral injuries(PFUI)result from traumatic disruption of the urethra.A significant proportion of cases are complex rendering their management challenging.We described management strategies for eight different complex PFUI scenarios.Methods:Our centre is a tertiary referral centre for complex PFUI cases.We maintain a prospective database(1995e2016),which we retrospectively analysed.All patients with PFUI managed at our institute were included.Results:Over two decades 1062 cases of PFUI were managed at our institute(521 primary and 541 redo cases).Most redo cases were referred to us from other centres.Redo cases had up to five prior attempts at urethroplasty.We managed complex cases,which included bulbar ischemia,young boys and girls with PFUI,PFUI with double block,concomitant PFUI and iatrogenic anterior urethral strictures.Bulbar ischemia merits substitution urethroplasty,most commonly,using pedicled preputial tube.PFUI in young girls is usually associated with urethrovaginal fistula.Young boys with PFUI commonly have a long gap necessitating trans-abdominal approach.Our success rate with individualised management is 85.60%in primary cases,79.13%in redo cases and 82.40%in cases of bulbar ischemia.Conclusion:The definition of complex PFUI is ever expanding.The best chance of success is at the first attempt.Anastomotic urethroplasty for PFUI should be performed in experienced hands at high volume centres.

A brief review on anterior urethral strictures

The treatment of urethral strictures remains a challenging field in urology even though there are a variety of procedures to treat it at present,as no one approach is superior over another.This paper reviewed the surgical options for the management of different sites and types of anterior urethral stricture,providing a brief discussion of the controversies regarding this issue and suggesting possible future advancements.Among the existing procedures,simple dilation and direct vision internal urethrotomy are more commonly used for short urethral strictures(<1 cm,soft and no previous intervention).Currently,urethroplasty using buccal mucosa or penile skin is the most widely adopted clinical techniques and have proved successful.Nonetheless,complications such as donor site morbidity remain problem.Tissue engineering techniques are considered as a promising solution for urethral reconstruction,but require further investigation,as does stem cell therapy.

Double‑Layer Nanofibrous Sponge Tube via Electrospun Fiber and Yarn for Promoting Urethral Regeneration

Insufficient bionic performance is a structural obstacle and makes urethral repair unobtainable.To overcome this challenge,we mimicked the urethral matrix and applied two electrospinning techniques to build a double-layer sponge tube of nanofib-ers and nanoyarns.Intriguingly,silk fibroin(SF)and vitamin B5(VitB5)could be introduced to increase the elasticity of the outer layer and reduce the hydrophobicity to further improve mesenchymal cell proliferation.Systematic experiments validated the bionic structure,biocompatibility,and exosome delivery capacity in this scaffold.We achieved scarless urethral repair by delivering the bioactive growth factors from adipose-derived stem cell exosomes by physical absorption.Biological regeneration of the urethra can be accomplished with continuous epithelium in animals.Furthermore,bioinformatics studies revealed that the expression of cell proliferation and fibrotic genes(e.g.,Wnt7a,cfa-miR-574)was responsible for the bio-logical regeneration of the adipose-derived stem cells exosomes(ADSC-exos)by delivering poly l-lactide-co-caprolactone/SF/VitB5 bilayer sponge(PSVBS)via reduced fibrosis gene expression,as well as improved epithelial formation and blood vessel formation.Therefore,the PSVBS design appeared to be an instructive approach for urethral and other tubular organ regeneration.

Histopathological changes of free buccal mucosa and colonic mucosa grafts after translation to dog bladder

Over the past years, more cases using buccal mucosa for urethral reconstruction have been reported.(1-4) The excellent early results with this tissue led some authors to extend their indications for its use. However, patients with complex, long-segment urethral strictures and significant scar tissue formation after the failure of previous urethroplasty, still present an operative challenge. The buccal mucosa may not be useful for the treatment of the complicated lengthy urethral strictures because of limited material. To explore the possibility of urethral reconstruction with a graft of colonic mucosa for the treatment of complicated lengthy strictures, we investigated the use of colonic mucosa as a novel substitute for urethral reconstruction in dogs with severe lengthy urethral structure.(5,6) The objects of the present study were to investigate further whether the colonic mucosal graft is an ideal substitute material, for urethral reconstruction, in place of buccal mucosal graft and their pathological characteristic after long-term exposure to urine.